Tizanidine is pharmacologically characterized as a central-acting α2 adrenoceptor agonist which has various pharmacological activities. The imidazoline chemical structure of tizanidine is related to other α2-adrenergic agonists.
Tizanidine can be classified generically as an amino-imidazoline adrenergic agent. In chemical nomenclature the molecule is described as 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole and is also identified with Chemical Abstracts Registry number 51322-75-9. Synthesis of the compound is disclosed in U.S. Pat. Nos. 3,843,668 and 4,053,617. Tizanidine hydrochloride is currently approved by the US Food and Drug Administration for the treatment of spasticity.
Presently, an immediate release formulation of tizanidine hydrochloride is dosed orally up to three times a day. This frequent oral dosing may lead to large fluctuations in the release profile of tizanidine hydrochloride, and subsequently, large fluctuations in the blood serum concentration of tizanidine. Side effects of immediate release tizanidine hydrochloride, such as somnolence, may be related to either the fluctuations in tizanidine concentration or excessively high tizanidine concentration, or both. A modified release formulation of tizanidine hydrochloride is approved in some European countries, but this modified release tizanidine hydrochloride has not shown any significant reduction in tizanidine hydrochloride side effects. A controlled release formulation of tizanidine should enable better command over the release profile and consequently, the blood serum concentration of tizanidine. While simply reformulating tizanidine in a modified release formulation has failed to achieve a significant reduction in side effects, applicants have discovered formulations and methods which tailor the tizanidine dose to reduce side effects.